Publications

PURPOSE

To examine the prevalence of unhealthy behaviors among a cohort of Vietnamese adolescents in California; to examine the relationship between these behaviors and school-related variables (school performance, educational risk behaviors, higher-education aspirations, and participation in extracurricular activities); and to assess the differences that may exist between males and females with regard to these factors.

METHODS

We conducted telephone interviews with 783 Vietnamese adolescents, aged 12-17 years, recruited through telephone listings from four California counties where large Vietnamese populations reside: San Francisco, Santa Clara, Los Angeles, and Orange. Of the 783 completed interviews, 60.8% were conducted in English and 39.2% in Vietnamese. The main outcome measure is a health risk behavior scale that includes adolescents' reports of ever smoking a cigarette, sedentary vs. active lifestyle, consumption of fruits and vegetables, consumption of foods high in fat, ever drinking alcohol, and ever engaging in sexual behavior. Multiple regression analyses were employed to estimate the association among the demographic variables, acculturation, school performance, aspirations, extracurricular activities, and the overall health risk.

RESULTS

Females were significantly more sedentary than males. Over one-quarter (29%) of the females reported not having participated in vigorous physical activity on 3 or more days per week, compared with just 18% of the males. Most adolescents reported they had never tried cigarettes (84%), never used alcohol (77%), and never had sex (97%). Males were more likely than females to report a higher frequency of experimentation with smoking and drinking. Overall, school performance and participation in extracurricular activities were significantly related to the health risk behavior scale. Adolescents who demonstrated at least one educational risk (ever skipped school or ever sent out of the classroom) were more likely to engage in other risky behaviors. Also, older and more acculturated adolescents were at increased risk of engaging in health-compromising behaviors. Analysis by gender revealed that the variables age, educational risk, and chance of attending college were all related to health risk behavior for both males and females. Among the boys, those who reported achieving an average grade of B or better had a decreased risk of engaging in health-compromising behaviors; however, neither extracurricular activities nor acculturation was related to health-compromising behaviors in boys. Among the girls, the reverse was true: lack of participation in extracurricular activities was related to health-compromising behaviors, whereas grades were not a significant risk factor.

CONCLUSIONS

Among sampled Vietnamese adolescents in California, health risk behaviors are common and inversely related to some school performance indicators. Using these indicators to identify high-risk groups could allow targeted educational programs or interventions for the mitigation of health-compromising behaviors.

Although hepatic myofibroblast migration plays a key role in the liver's injury response, the signal transduction pathways mediating the migration of this cell type are uncertain. Recently, we reported that lysophosphatidic acid (LPA) stimulates the migration of hepatic myofibroblasts. The goal of this study was to test the hypothesis that rho and p38 MAP kinase signaling pathways mediate LPA-stimulated hepatic myofibroblast migration. We measured migration, myosin regulatory light chain and p38 MAP kinase phosphorylation, and contractile force generation by human hepatic myofibroblasts. LPA stimulated migration in a dose-dependent and saturable manner that was partially blocked by Y-27632, a rho-associated kinase inhibitor, as well as by SB-202190, a p38 MAP kinase inhibitor. LPA also induced myosin regulatory light chain phosphorylation and contractile force generation in a Y-27632 dependent, and SB-202190 independent fashion. Moreover, LPA stimulated a dose-dependent and saturable phosphorylation of p38 MAP kinase, which was not altered by Y-27632 or C3 transferase, a rho inactivator. These novel results suggest that LPA stimulates hepatic myofibroblast migration via distinct pathways that signal through rho and p38 MAP kinase.

Familial hypercholanemia (FHC) is characterized by elevated serum bile acid concentrations, itching, and fat malabsorption. We show here that FHC in Amish individuals is associated with mutations in tight junction protein 2 (encoded by TJP2, also known as ZO-2) and bile acid Coenzyme A: amino acid N-acyltransferase (encoded by BAAT). The mutation of TJP2, which occurs in the first PDZ domain, reduces domain stability and ligand binding in vitro. We noted a morphological change in hepatic tight junctions. The mutation of BAAT, a bile acid-conjugating enzyme, abrogates enzyme activity; serum of individuals homozygous with respect to this mutation contains only unconjugated bile acids. Mutations in both TJP2 and BAAT may disrupt bile acid transport and circulation. Inheritance seems to be oligogenic, with genotype at BAAT modifying penetrance in individuals homozygous with respect to the mutation in TJP2.

Coronary heart disease is a major cause of death in Europe and the USA. Insudation of atherogenic lipoproteins, including low-density lipoprotein (LDL), into the artery wall is integral to atherosclerosis. It is clear that numerous genetic loci contribute to increased plasma levels of LDL. However, five specific monogenic disorders, three of which have been reported recently, are known to increase LDL. These are familial hypercholesterolemia (LDL receptor gene: LDLR); familial ligand-defective apoB- 100 (apoB gene: APOB); autosomal recessive hypercholesterolemia (ARH gene); sitosterolemia (ABCG5 or ABCG8 genes) and cholesterol 7alpha-hydroxylase deficiency (CYP7A1 gene). This review relates the mechanisms underlying these five disorders with specific therapeutic interventions.

Nuclear hormone receptors are ligand-dependent transcription factors. The class of nuclear hormone receptors that form heterodimers with retinoid X receptor includes members that are well established targets of current dermatological therapeutics such as the retinoic acid receptor (RAR) and the vitamin D receptor (VDR) as well as more recently discovered receptors including the peroxisome proliferator-activated receptors (PPAR) and the liver X receptor (LXR). After ligand activation (often lipid metabolites), these intracellular receptors exert their functions by binding to specific response elements in regulatory sequences of target genes, preferentially those involved in differentiation, energy expenditure and lipid metabolism. A number of selective activators has been developed by combinational chemistry, initially for their anti-diabetic and lipid lowering properties as well as their ability to regulate bile acid and drug metabolism. However, these activators also have marked effects on cutaneous homeostasis. Therefore, these compounds have important implications for dermatological therapy. In this review, the clinical implications of the more recently discovered members of the nuclear hormone receptor family are discussed.

The only known function of human sebaceous glands is the provocation of acne. We assessed here whether sebum influences stratum corneum hydration or permeability barrier function in asebia J1 and 2 J mice, with profound sebaceous gland hypoplasia. Asebia J1 mice showed normal permeability barrier homeostasis and extracellular lamellar membrane structures, but they displayed epidermal hyperplasia, inflammation, and decreased (>50%) stratum corneum hydration, associated with a reduction in sebaceous gland lipids (wax diesters/monoesters, sterol esters). The triglyceride content of both asebia and control stratum corneum was low, consistent with high rates of triglyceride hydrolysis within the normal pilosebaceous apparatus, despite high rates of triglyceride synthesis. Although a mixture of synthetic, sebum-like lipids (sterol/wax esters, triglycerides) did not restore normal stratum corneum hydration to asebia skin, topical glycerol, the putative product of triglyceride hydrolysis in sebaceous glands, normalized stratum corneum hydration, and the glycerol content of asebia stratum corneum was 85% lower than in normal stratum corneum. In contrast, another potent endogenous humectant (urea) did not correct the abnormality. The importance of glycerol generation from triglyceride in sebaceous glands for stratum corneum hydration was demonstrated further by (i) the absence of sebaceous-gland-associated lipase activity in asebia mice, whereas abundant enzyme activity was present in the glands of control mice; and (ii) the inability of high concentrations of topical triglyceride to correct the hydration abnormality, despite the presence of abundant lipase activity in asebia stratum corneum. These results show that sebaceous-gland-derived glycerol is a major contributor to stratum corneum hydration.

The upper airway, including nasal cavities, naso-, oro-, and hypopharynx, is the portal of entry for air pollutants. Upper airway (as well as eye) irritation figures prominently in symptom reporting in so-called problem buildings and with exposure to environmental tobacco smoke. Large particles and water-soluble gases and vapors are likely to have their initial irritant effects in the mucous membranes of the upper airway and eyes, giving warning to the exposed individual to minimize further exposure. The spectrum of irritant-related upper airway health effects is reviewed in this article.

PURPOSE

To study the association of physician characteristics, the characteristics of their practice settings, patient mix, and reported frequency of prescribing asthma medication with patients' health status and health-related quality of life in asthma.

METHODS

We conducted a mail-back survey of physicians (n = 147) that included demographic characteristics, practice and training characteristics, and reported prescribing frequencies for common asthma treatments. We also conducted structured telephone interviews with 317 of their patients, assessing demographic characteristics, health status (as measured by the Short Form-12 [SF-12] physical component score), and asthma-specific quality of life (as measured by the Marks questionnaire).

RESULTS

In adjusted analyses, pulmonary specialists were more likely to report using leukotriene modifiers (odds ratio [OR] = 4.7; 95% confidence interval [CI]: 1.2 to 18) and theophylline (OR = 3.0; 95% CI: 1.0 to 9.0) in adult patients with asthma. Working in a practice of >75% health maintenance organization (HMO)- or preferred provider organization (PPO)-insured patients was associated with a lower likelihood of prescribing leukotriene modifiers (OR = 0.1; 95% CI: 0.01 to 0.5). Adjusting for patient demographic characteristics and steroid dependence, physician prescribing tendencies were not associated with patients' perceived health status or quality of life. Although an HMO- or PPO-predominant practice was associated with better physical health status (mean difference in SF-12 physical component score, 3.1; 95% CI: 0.05 to 6.2; P = 0.05), there was no statistical association with quality of life.

CONCLUSION

The characteristics of physicians, their practices, and the asthma medication prescribing strategies that they adopt are not strongly associated with patients' perceived outcomes.

Carrageenan-induced inflammatory pain lasting hours to days produces a protein kinase C epsilon (PKC epsilon )-dependent 'primed' state lasting several weeks, during which time injection of prostaglandin E2 induces hyperalgesia which is markedly enhanced and prolonged compared to PGE2-induced hyperalgesia in normal 'unprimed' rats. In the present study, we demonstrate that while inhibition of prostaglandin synthesis and antagonism of beta2-adrenergic receptors markedly attenuated the hyperalgesia induced by carrageenan, these interventions did not affect hyperalgesic priming. Tumor necrosis factor-alpha (rat recombinant; rrTNFalpha), another mediator of carrageenan-induced inflammation, alone produced hyperalgesia and priming, which were attenuated and prevented, respectively, by intrathecal administration of antisense to PKC epsilon. Inhibition of TNFalpha with thalidomide or a rat polyclonal anti-TNFalpha antibody attenuated carrageenan-induced hyperalgesia and prevented priming. Intrathecal administration of antisense to tumour necrosis factor receptor type-1 (TNFR1) reduced the level of TNFR1 transported toward the peripheral terminals of sensory neurons, and attenuated both carrageenan- and rrTNFalpha-induced priming. Acute hyperalgesia induced by carrageenan or rrTNFalpha remained intact in animals treated with TNFR1 antisense. Our results demonstrate that the generation of the primed state does not require production of hyperalgesia and that TNFalpha, which is generated during acute inflammation, can act on sensory neurons to induce hyperalgesic priming by activating neuronal PKC epsilon.

Subdiaphragmatic vagotomy produces a decrease in mechanical nociceptive threshold that is greater in male rats and an enhancement of bradykinin hyperalgesia that is greater in female rats. To examine the role of gonadal hormones in these sex differences, we evaluated the effect of gonadectomy, with or without gonadal hormone replacement, on vagal modulation of nociceptive threshold and bradykinin hyperalgesia by using the Randall-Selitto paw withdrawal test. Gonadectomy (before sexual maturation) plus vagotomy decreased nociceptive threshold in male rats more than either lesion alone, whereas neither lesion nor in combination had an effect on nociceptive threshold in female rats. Testosterone or dihydrotestosterone replacement in gonadectomized plus vagotomized males and 17 beta-estradiol in females did not significantly alter nociceptive threshold compared to vagotomy plus gonadectomy, respectively. Combined vagotomy and gonadectomy unexpectedly almost completely abolished bradykinin hyperalgesia, whereas gonadectomy alone had no effect on bradykinin hyperalgesia in both sexes. Testosterone replacement in vagotomized males and 17 beta-estradiol in vagotomized females reversed the effect of gonadectomy. Dihydrotestosterone replacement in vagotomized males also reversed the effect of gonadectomy on bradykinin hyperalgesia, although to a lesser degree than testosterone. We conclude that although gonadal hormones and other gonadal-dependent mechanisms influence nociception, they do not account for sexual dimorphism in vagal modulation of mechanical nociceptive threshold or bradykinin hyperalgesia.